The primary focus is to examine the neurophysiologic basis of the respiratory-motor coupling and to rule out potential alternatives. We hypothesize that there is a finger flexion-expiration, finger extension-inspiration coupling. The neurophysiologic basis for this coupling is that forced expiration enhances corticospinal excitability for the finger flexors and finger extensors, while forced inspiration enhances activation primarily for the finger extensors. To test the hypothesis, we will quantify changes in corticospinal excitability associated with voluntary breathing (Aim 1) using transcranial magnetic stimulation (TMS) and neuromuscular electrical stimulation (ES) in a variety of tasks in normal subjects. In Aim 2, we will investigate potential alternative mechanisms that the voluntary breathing effects are artifacts of mechanical transfer or of dual tasking. Collectively, outcomes of this project are likely to provide evidence for the intrinsic neurophysiologic basis of the finger flexion-expiration, finger extension-inspiration coupling. The long-term goal is to apply the intrinsic physiological coupling between voluntary breathing and finger muscles to rehabilitation of finger extension impairment after stroke, e.g. electrical stimulation delivered to the finger extensors on the inspiratory phase of voluntary breathing is expected to maximize the stimulation effect. PUBLIC HEALTH RELEVANCE: The proposed research examines underlying neurophysiologic mechanisms of the respiratory-motor coupling using non-invasive tools will be used, such as transcranial magnetic stimulation (TMS) and neuromuscular electrical stimulation (ES). The potential alternative mechanisms will be ruled out. Potential clinical applications of this newly discovered phenomenon for stroke rehabilitation are demonstrated.